Individuals with aphasia, a disorder caused by damage to language-related brain regions, are often afflicted with speech production difficulties that greatly impair communication. The goal of this K99/R00 Pathway to Independence Award is to provide the candidate, Dr. Caroline Niziolek, with a strong grounding in patient- based research and cutting-edge neural connectivity analysis, enabling her to apply her expertise in speech motor control to investigate the functional abnormalities at the root of this communication disorder. In this proposal, Dr. Niziolek aims to identify the neurophysiological causes of speech production deficits in aphasia and to assess whether feedback-based speech training can ameliorate them. Her recent neuroimaging research in healthy speakers suggests that the auditory system constantly monitors its own speech for small deviations from intended speech sounds, and that successful monitoring may drive an unconscious motor correction of these deviations before they are realized as errors. The central hypothesis of this project is that in speakers with aphasia, production deficits may be due to a failure of detection: that is, the auditory system is not sensitive to an aphasic speaker's own deviations until after they become full-blown speech errors. Importantly, in testing this hypothesis, Dr. Niziolek will look across aphasic patients, regardless of their lesion location or clinically-defined subtype, using an objective neural marker she developed to assess detection ability. Her immediate goal for the K99 phase is to use this neural marker, along with behavioral metrics, to characterize each individual's deficit as either perceptual (difficulty detecting one's own errors) or motor (preservd ability to detect errors but difficulty in carrying out corrective commands). She will then relate these objectively-measured deficits to patterns of lesions and magnetoencephalographic (MEG) connectivity to determine the structural and functional network abnormalities that cause each type of deficit. With this understanding, she plans to carry out a novel speech production training study in the R00 phase of the award. The proposed speech training game uses a visual cursor that is mapped to acoustic input so that participants can use their voice to move the cursor to a visual target. The target will correspond to the production of a given speech sound, such as the e in bed. This training provides a secondary source of sensory feedback for the detection of deviations from a target. By training aphasic patients to learn to hit vocal targets using visual feedback, Dr. Niziolek aims to use an intact system (vision) to retrain the damaged one (auditory detection). Her long-term goal is to use this paradigm in conjunction with the neural marker assessment to develop personalized treatments that are tailored to each patient's specific functional deficit (auditory detection or motor correction). This research career development plan will be carried out at Boston University with an impressive co-mentor team from whom she will gain invaluable clinical and technical training, with the ultimate aim of developing a translational research program that can be extended to other speech disorders.